Clinical Trials /

A Phase 2 Study of Pembrolizumab in Patients With Histiocyte/Dendritic Cell Neoplasms and Biologically Selected Subtypes of Relapsed/Refractory Aggressive Lymphomas

NCT03316573

Description:

This research study is studying a drug called pembrolizumab as a possible treatment for aggressive lymphoma or a histiocyte or dendritic cell neoplasm. The drug involved in this study is: -Pembrolizumab

Related Conditions:
  • Angioimmunoblastic T-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Dendritic Cell Sarcoma
  • Histiocytic Sarcoma
  • Interdigitating Dendritic Cell Sarcoma
  • Plasmablastic Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of Pembrolizumab in Patients With Histiocyte/Dendritic Cell Neoplasms and Biologically Selected Subtypes of Relapsed/Refractory Aggressive Lymphomas
  • Official Title: A Phase 2 Study of Pembrolizumab in Patients With Histiocyte/Dendritic Cell Neoplasms and Biologically Selected Subtypes of Relapsed/Refractory Aggressive Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 17-448
  • NCT ID: NCT03316573

Conditions

  • Lymphoma
  • Histiocytic Sarcoma
  • Follicular Dendritic Cell Sarcoma
  • Interdigitating Dendritic Cell Sarcoma

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab

Purpose

This research study is studying a drug called pembrolizumab as a possible treatment for aggressive lymphoma or a histiocyte or dendritic cell neoplasm. The drug involved in this study is: -Pembrolizumab

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this
      specific disease but it has been approved for other uses.

      The study drug is an antibody that targets a molecule called PD-1. PD-1 is used to turn down
      the immune system. In general, this is used by the body to prevent the immune system from
      being too active. However, several cancers appear to use this pathway to prevent the immune
      system from attacking them. The theory behind this study is that by blocking PD-1, we may be
      able to prevent the cancer from hiding from the immune system and allow the immune system to
      attack the cancer more effectively. There is evidence that the type of lymphoma the
      participant have may use PD-1 to escape the immune system.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalPembrolizumab will be administered intravenously every 3 weeks for 35 cycles
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent for the trial.

          -  Histologically confirmed diagnosis of a histiocyte/dendritic cell neoplasm or
             relapsed/refractory aggressive lymphoma with at least one of the following features
             (with review required at a participating study center):

               -  Diffuse large B cell lymphoma with EBV positive tumor cells (defined as positive
                  EBV-encoded RNA in tumor cells)

               -  Plasmablastic lymphoma

               -  T cell/histiocyte rich DLBCL

               -  EBV+ T cell lymphoma of any histology; note, patients with angioimmunoblastic T
                  cell lymphoma will be eligible regardless of EBV status

               -  Histiocytic sarcoma

               -  Follicular dendritic cell sarcoma

               -  Interdigitating dendritic cell sarcoma

          -  For patients with histiocytic sarcoma, interdigitating dendritic cell sarcoma, or
             follicular dendritic cell sarcoma only: disease that is not amenable to surgical
             resection and/or radiation therapy with curative intent.

          -  For lymphoma patients only: At least one prior systemic chemotherapy including an
             alkylating agent and anthracycline (unless contraindicated), and an anti-CD20
             monoclonal antibody if the tumor is CD20+.

          -  For lymphoma patients only: Participants must have received and relapsed after
             autologous stem cell transplantation (ASCT), or be ineligible for ASCT (including on
             the basis of refractory disease), or have declined ASCT

          -  Age 18 years or older at the time of signing consent.

          -  ECOG performance status of 0 or 1 (Karnofsky ≥70%, see Appendix A)

          -  Participants must have normal organ and marrow function as defined below:

               -  absolute neutrophil count ≥ 1,000/mcL

               -  platelets ≥75,000/mcL (> 30,000 if there is bone marrow involvement with
                  lymphoma)

               -  total bilirubin < 1.5 times the institutional upper limit of normal (ULN) OR
                  direct bilirubin < the normal in subjects with total bilirubin >1.5 times the ULN

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or < 5 times ULN in patients with
                  known hepatic involvement with lymphoma

               -  albumin > 2.5 mg/dl

               -  creatinine < 1.5 times the normal upper institutional limit OR creatinine
                  clearance ≥60 mL/min/1.73 m2 in participants with creatinine levels > 1.5 times
                  the normal upper institutional limit

               -  INR, aPTT or PT < 1.5 times the ULN unless subject is receiving anticoagulation
                  therapy as long as PT or aPTT are within therapeutic range of intended use of
                  anticoagulant

          -  Be willing to provide tissue from a newly obtained core needle or excisional biopsy.
             Newly-obtained is defined as a specimen obtained up to and including 90 days prior to
             treatment day 1. Subjects for whom newly obtained samples cannot be provided may be
             enrolled only with agreement by the overall PI.

          -  No prior allogeneic transplant unless all of the following apply:

               -  At least 5 years from time of transplant

               -  Absence of clinically significant graft-versus-host disease (GVHD)

               -  Not on immune suppression

               -  Approval of overall PI

          -  Not a candidate for potentially curative therapy at the time of enrollment

          -  Measurable disease per the Lugano criteria.

          -  Female subjects of childbearing potential should have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study medication.
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required.

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception as outlined in Section 5.4.3 - Contraception for the course of the study
             through 120 days after the last dose of study medication.

          -  Abstinence is acceptable if this is the usual lifestyle and preferred contraception
             for the subject.

          -  Male subjects of childbearing potential must agree to use an adequate method of
             contraception as outlined in Section 5.4.3- Contraception, starting with the first
             dose of study therapy through 120 days after the last dose of study therapy.

          -  Abstinence is acceptable if this is the usual lifestyle and preferred contraception
             for the subject

          -  The effects of pembrolizumab on the developing human fetus are unknown. Should a woman
             become pregnant or suspect she is pregnant while she or her partner is participating
             in this study, she should inform her treating physician immediately.

        Exclusion Criteria:

          -  Prior treatment with a PD-1, PD-L1 or PD-L2 inhibitor

          -  Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study day 1 or
             has not recovered (i.e., < grade 1 or at baseline) from adverse events due to a
             previously administered agent.

          -  Participants who have had chemotherapy, targeted small molecule therapy, or
             radiotherapy within 2 weeks prior to study day 1 (6 weeks for nitrosoureas or
             mitomycin C) or who has not recovered (i.e., < grade 1 or at baseline) from adverse
             events due to previously administered agents. Note: subjects with < grade 2 peripheral
             neuropathy are an exception to this criterion and may qualify for the study.

          -  Radiation therapy within 2 weeks of study treatment

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          -  Has a known history of active tuberculosis

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Has an active infection requiring systemic therapy.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e., with the use of disease modifying agents, corticosteroids, or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal her pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive
             therapy within 7 days prior to the first dose of trial treatment or is taking chronic
             systemic steroids (in doses exceeding 10 mg daily of prednisone equivalent) within 7
             days prior to the first dose of trial treatment. Note: Subjects with asthma or chronic
             obstructive pulmonary disease that require intermittent use of bronchodilators,
             inhaled steroids, or local steroid injections are not excluded from the study.

          -  Has a history of non-infectious pneumonitis that required systemic corticosteroid
             treatment or has active pneumonitis.

          -  Known active central nervous system involvement and/or carcinomatous meningitis.
             Subjects with previously treated brain metastases may participate provided they are
             stable (without evidence of progression by imaging for at least 4 weeks prior to the
             first dose of trial treatment and any neurologic symptoms have returned to baseline),
             have no evidence of new or enlarging brain metastases, and are not using steroids for
             at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer

          -  Active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g.,
             hepatitis C virus RNA detectable).

          -  Human immunodeficiency virus (HIV 1/2).

          -  Is pregnant or breast-feeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit until 120 days
             after the last dose of trial treatment.

          -  Has received a live vaccine within 30 days of planned start of study therapy. (Note:
             seasonal influenza vaccines for injection are allowed as they are inactivated;
             however, intranasal influenza vaccines are live attenuated vaccines and are NOT
             allowed)

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to pembrolizumab.

          -  Baseline pulse oximetry <94% or requires oxygen supplementation of any kind

          -  If subject underwent major surgery they must have recovered adequately from the
             toxicity and/or complications from the procedure prior to starting therapy.

          -  Uncontrolled intercurrent illness including, but not limited to symptomatic congestive
             heart failure, unstable angina pectoris, or cardiac arrhythmia
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:The percentage of subjects with partial response and complete response by PET/CT scan

Secondary Outcome Measures

Measure:Complete Response Rate
Time Frame:2 years
Safety Issue:
Description:The percentage of patients with complete response
Measure:safety and toxicity
Time Frame:2 years
Safety Issue:
Description:the number of patients with an adverse event
Measure:Duration of Response
Time Frame:2 years
Safety Issue:
Description:the length of complete or partial response
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:amount of time subject is alive and without worsening disease
Measure:Duration of Complete Response
Time Frame:2 years
Safety Issue:
Description:the length of complete response
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:length of time from study entry until death (if applicable)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Lymphoma
  • Histiocyte sarcoma
  • Follicular Dendritic Cell Saroma
  • Interdigitating dendritic cell sarcoma

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